Pulmonary Thrombotic Microangiopathy Research Articles

Echocardiography Can Improve the Selection of Mechanical Support Strategies for Patients With Severe COVID-19 Respiratory Distress Syndrome.

To the Editor: I read with interest the study by Beyls et al.1 which compared the different clinical characteristics and outcomes of patients with COVID-19–related respiratory distress syndrome (CARDS) requiring veno-venous extracorporeal membrane oxygenation (VV-ECMO) during the three epidemic waves of COVID-19 in France. Despite the increasing knowledge on the particularities of severe COVID-19 and the growing experience in the management of severe CARDS, that study revealed a massive increase in the 90 day mortality of patients undergoing VV-ECMO during the second epidemic wave. One plausible explanation for that important observation could be the fact that over the course of the pandemic, new variants of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have continuously emerged. Because the different waves of infection were mainly associated with one or more SARS-CoV-2 “variants of concern” (VOC) with different pathogenicity, it appears obvious that the pathogenicity of the dominant VOC in an infection wave can have important impacts on the outcomes of patients with severe COVID-19. Indeed, the Delta/B.1.617.2 variant, which was dominant during the second wave, is known to be associated with higher risk of death than both the previously dominant VOCs (i.e., Alpha/B.1.1.7, Beta/B.1.351 and Gamma/P.1) and the Omicron/B1.1.529 variant which became the dominant VOC during third wave.2,3 The excessively high mortality rate (i.e., 85.7%1) of patients supported by ECMO during the second wave deserves particular attention because a renewed appearance of more pathogenic VOCs cannot be ruled out. The high incidence of extensive pulmonary thrombotic microangiopathy associated with severe ventilation-perfusion mismatch, increased resistance in the pulmonary circulation and frequent afterload-induced right ventricular (RV) failure, which were identified as distinct features of severe CARDS (especially in infections caused by the Delta/B.1.617.2 variant) were often the leading cause of death attributed to COVID-19.4,5 Early detection of patients with increasing RV hemodynamic overloading can facilitate the selection of the most appropriate management (including the requirement of ECMO or a combined respiratory and circulatory support), which can be decisive for the patients’ survival.4 In severe RV afterload mismatch, the RV output decreases substantially, and RV dilation-related tricuspid regurgitation can rapidly increase. In such situations, attempting to treat the underlying etiology of impaired gas exchange using VV-ECMO alone may become insufficient.4 Considering the high incidence and the deleterious prognostic impact of right heart involvement in severe COVID-19 it seems likely that this was also the major cause of the high mortality rate documented by Beyls et al.1 for their ECMO-supported patients (92% with VV-ECMO) during the second wave. Thus, close monitoring of the right heart in patients with CARDS associated with hemodynamic instability, already before overt RV failure develops, could substantially improve therapeutic decision-making. It is therefore difficult to understand the still limited use of routine echocardiography for the surveillance of hospitalized patients with COVID-19. Echocardiography can improve the identification of patients with CARDS requiring ECMO therapy, the selection of the most appropriate support strategy (VV-ECMO, veno-arterial-ECMO, or VV-ECMO plus RV or left ventricle temporary percutaneous mechanical support) and also the weaning decision-making after cardiopulmonary amelioration during the support.

Features of the clinical presentation and course of community-acquired pneumonia against the background of type 2 diabetes mellitus

Community-acquired pneumonia remains the leading infectious cause of death around the world. Many factors influence the prognosis and outcome of this disease. Compared with healthy individuals, patients with diabetes mellitus are at increased risk of respiratory tract infections, such as community-acquired pneumonia. Diabetes mellitus contributes to the development of pulmonary thrombotic microangiopathy, changing the functional state of the lungs. In numerous studies involving patients with diabetes mellitus, data on the state of the lungs were obtained by instrumental tests, such as spirometry, ventilation / perfusion scintigraphy, perfusion computed tomography, and diffusing capacity of the lungs for carbon monoxide. In patients with community-acquired pneumonia, diabetes mellitus causes vague clinical symptoms, leads to a severe course of the disease, and contributes to development of complications. Diagnosing the functional state of the lungs in patients with community-acquired pneumonia against the background of diabetes mellitus has not been studied.

COVID-19 and Dialysis Patients: Unsolved Problems in Early 2021.

COVID-19 and Dialysis Patients: Unsolved Problems in Early 2021.

Pathological Findings in COVID-19 as a Tool to Define SARS-CoV-2 Pathogenesis. A Systematic Review.

Introduction: The World Health Organization declared the COVID-19 pandemic in March 2020. COVID-19 still represents a worldwide health emergency, which causesa severe disease that has led to the death of many patients. The pathophysiological mechanism of SARS-CoV-2 determining the tissue damage is not clear and autopsycan be auseful tool to improve the knowledge of this infection and, thus, it can help achieve a timely diagnosis and develop an appropriate therapy. This is an overview of the main post-mortem findings reporting data on the infection effects on several organs. Methods: A systematic literature search was conducted in the PubMed database searching for articles from 1 January to August 31, 2020. Thearticles were selected identifying words/concepts in the titles and/or abstracts that indicated the analysis of the morphological/pathological tissue injuries related to SARS-CoV-2 disease by several investigations. Results: A total of 63 articles were selected. The main investigated tissue was the lung showing a diffuse alveolar damage (DAD) frequently associated with pulmonary thrombotic microangiopathy. Inflammatory findings and vascular damage were observed in other organs such as heart, liver, kidney, brain, spleen, skin and adrenal gland. The immunohistochemical analysis showed tissue inflammatory cells infiltrates. The virus presence was detected by several investigations such as RT-PCR, immunohistochemistry and electron microscope, showing the effect ofSARS-CoV-2not exclusively in the lung. Discussion: The evidence emerging from this review highlighted the importance of autopsy to provide a fundamental base in the process of understanding the consequences ofSARS-CoV-2 infection. COVID-19 is strictly related to a hyper inflammatory state that seems to start with DAD and immuno-thrombotic microangiopathy. Massive activation of the immune system and microvascular damage might also be responsible for indirect damage to other organs, even if the direct effect of the virus on these tissues cannot be excluded.

Postmortem examination of COVID-19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings in lungs and other organs suggesting vascular dysfunction.

AimsCoronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has rapidly evolved into a sweeping pandemic. Its major manifestation is in the respiratory tract, and the general extent of organ involvement and the microscopic changes in the lungs remain insufficiently characterised. Autopsies are essential to elucidate COVID‐19‐associated organ alterations.Methods and resultsThis article reports the autopsy findings of 21 COVID‐19 patients hospitalised at the University Hospital Basel and at the Cantonal Hospital Baselland, Switzerland. An in‐corpore technique was performed to ensure optimal staff safety. The primary cause of death was respiratory failure with exudative diffuse alveolar damage and massive capillary congestion, often accompanied by microthrombi despite anticoagulation. Ten cases showed superimposed bronchopneumonia. Further findings included pulmonary embolism (n = 4), alveolar haemorrhage (n = 3), and vasculitis (n = 1). Pathologies in other organ systems were predominantly attributable to shock; three patients showed signs of generalised and five of pulmonary thrombotic microangiopathy. Six patients were diagnosed with senile cardiac amyloidosis upon autopsy. Most patients suffered from one or more comorbidities (hypertension, obesity, cardiovascular diseases, and diabetes mellitus). Additionally, there was an overall predominance of males and individuals with blood group A (81% and 65%, respectively). All relevant histological slides are linked as open‐source scans in supplementary files.ConclusionsThis study provides an overview of postmortem findings in COVID‐19 cases, implying that hypertensive, elderly, obese, male individuals with severe cardiovascular comorbidities as well as those with blood group A may have a lower threshold of tolerance for COVID‐19. This provides a pathophysiological explanation for higher mortality rates among these patients.

Renal and pulmonary thrombotic microangiopathy triggered by proteasome-inhibitor therapy in patient with smoldering myeloma

Rationale:Thrombotic microangiopathy (TMA) is a group of clinical syndromes characterized by excessive platelet activation and endothelial injury that leads to acute or chronic microvascular obliteration by intimal mucoid and fibrous thickening, with or without associated thrombi. It frequently involves the kidney but may involve any organ or system at variable frequencies depending on the underlying etiology. Among its numerous causes, drug toxicities and complement regulation abnormalities stand out as some of the most common. A more recently described association is with monoclonal gammopathy. Lung involvement by TMA is infrequent, but has been described in Cobalamin C deficiency and post stem-cell transplantation TMA.Patient concerns:This is the case of a patient with smoldering myeloma who received proteasome-inhibitor therapy due to retinopathy and developed acute renal failure within one week of therapy initiation.Diagnoses:A renal biopsy showed thrombotic microangiopathy. At the time, mild pulmonary hypertension was also noted and presumed to be idiopathic.Interventions:Given the known association of proteasome-inhibitor therapy with thrombotic microangiopathy, Bortezomib was discontinued and dialysis was initiated.Outcomes:Drug withdrawal failed to prevent disease progression and development of end-stage renal disease, as well as severe pulmonary hypertension that eventually lead to the patient's death.Lessons:To our knowledge, this is the first reported case of pulmonary involvement by TMA associated with monoclonal gammopathy which appears to have been triggered by proteasome-inhibitor therapy. Clinicians should be aware of this possibility to allow for more prompt recognition of pulmonary hypertension as a potential manifestation of monoclonal gammopathy-associated TMA, especially in patients also receiving proteasome-inhibitors, so that treatment aiming to slow disease progression can be instituted.